Thorac Cardiovasc Surg 2014; 62 - OP127
DOI: 10.1055/s-0034-1367201

Human endothelial-colony forming cells enhance cardiac repair by increasing neovascularization and the pool of Sca1+ cardiac resident stem cells after myocardial infarction in SCID/beige mice

M.-A. Deutsch 1, 2, B. Huber 2, G. Assmann 3, J. Müller-Höcker 3, I. Ott 4, W.-M. Franz 2, 5
  • 1Deutsches Herzzentrum München, Klinik für Herz- und Gefäßchirurgie, München, Germany
  • 2Klinikum der LMU Großhadern, Medizinische Klinik und Poliklinik I, München, Germany
  • 3Pathologisches Institut der LMU München, Campus Großhadern, München, Germany
  • 4Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, München, Germany
  • 5Medizinische Universitätsklinik Innsbruck, Klinik für Innere Medizin III / Kardiologie und Angiologie, Innsbruck, Austria

Objective: The potential therapeutic role of EPCs in ischemic heart disease is subject to intense investigation. It has been shwon that the transplantation of unfractioned bone marrow stem cells after myocardial infarction (MI) is moderately effective. Selected stem cell populations may further optimize treatment. The aim of the study was to investigate the proregenerative potential of human endothelial colony-forming cells (ECFCs) in a murine MI model.

Methods: CD34+ peripheral blood mononuclear cells were isolated from patient blood samples using immunomagnetic beads. For generating ECFCs, CD34+ cells were plated on fibronectin-coated dishes and were expanded by culture in endothelial-specific cell medium. Either human ECFCs (5 × 10 (5)) or control medium were injected into the peri-infarct region after surgical MI induction in SCID/beige mice. Hemodynamic function was assessed invasively 30 days post-MI. Hearts were analyzed immunohistochemically for assessing cell fate, infarct size and neovascularization (ECFCs n = 15 vs. control n = 10). Flow-cytometric analysis of enzymatically digested whole heart tissue was used to analyze different subsets of homing CD34+/CD45+ mononuclear cells as well as CD34-/CD45- cardiac resident stem cells 2 days post-MI (ECFCs n = 10 vs. control n = 10).

Results: Transplantation of human ECFCs after MI improved hemodynamic function at day 30 post-MI (EF: 30.43 ± 1.20% vs. 22.61 ± 1.73, p>0.001; dP/dTmax 5202.28 ± 316.68 mmHg/sec vs. 3896.24 ± 534.95, p < 0.05) when compared controls. Correspondingly, ECFCs significantly reduced infarct size (50.3 ± 4.5% vs. 66.1 ± 4.3, p < 0.05). Immunohistochemistry failed to show integration of transplanted cells. However, anti-CD31 immunohistochemistry proofed an increased vascular density within the infarct border zone (8.6 ± 0.4 per HPF vs. 6.2 ± 0.5, p < 0.001). Flow cytometry at day 2 post-MI showed a slight statistical trend towards increased myocardial homing of CD45+/CD34+ mononuclear cells (1.1 ± 0.3% vs. 0.7 ± 0.1, p = 0.2). Interestingly, we detected a significant increase in CD34-/CD45-/Sca1+ cardiac resident stem cells (11.7 ± 1.7% vs. 4.7 ± 1.7, p < 0.01).

Conclusions: In a murine MI model, transplantation of human ECFCs ameliorates myocardial function by improving adverse post-MI remodeling. Cardiac repair is enhanced by increasing myocardial neovascularization and the pool of Sca1+ cardiac resident stem cells. The use of human ECFCs for treating ischemic heart disease warrants further investigation.